Active, not recruiting
Phase 2
Enhanced Dermatological Care to Reduce Rash and Paronychia in Epidermal Growth Factor Receptor (EGRF)-Mutated Non-Small Cell Lung Cancer (NSCLC) Treated First-line With Amivantamab Plus Lazertinib
Condition(s) studied
Carcinoma, Non-Small-Cell Lung
Investigational drug(s) / intervention(s)
Amivantamab IVAmivantamab SCLazertinibDoxycyclineMinocyclineClindamycinChlorhexidineNoncomedogenic skin moisturizerRuxolitinibTacrolimusZinc gluconatePropranololTimololClobetasol
Amivantamab IV: Amivantamab will be administered.
Amivantamab SC: Amivantamab will be administered as SC injection.
Lazertinib: Lazertinib tablet will be administered orally.
Doxycycline: Doxycycline tablet will be administered orally.
Minocycline: Minocycline capsule will be administered orally.
Clindamycin: Clindamycin lotion will be used as topical application on the scalp.
Chlorhexidine: Chlorhexidine solution will be used as topical application on hands and feet.
Noncomedogenic skin moisturizer: Noncomedogenic skin moisturizer will be used as topical application.
Ruxolitinib: Ruxolitinib will be used to the affected skin area.
Tacrolimus: Tacrolimus will be used as topical application to the affected skin area.
Zinc gluconate: Zinc gluconate tablet will be administered.
Propranolol: Propranolol tablet will be administered.
Timolol: Timolol will be used to the affected skin area.
Clobetasol: Clobetasol shampoo will be used on the scalp.
Study summary
The purpose of this study is to evaluate whether enhanced dermatologic management can reduce incidence of grade greater than or equal to (\>=) 2 dermatologic adverse events of interest (DAEIs) when compared with standard-of-care skin management and with modified enhanced dermatologic management in participants with locally advanced or metastatic stage IIIB/C-IV epidermal growth factor receptor (EGFR)-mutated non-small cell lung cancer (NSCLC) treated first-line with amivantamab and lazertinib. The study also includes Expansion cohorts (in 2 different schedules) to evaluate enhanced dermatologic management and early intervention for DAEIs or paronychia, in participants receiving subcutaneous amivantamab and lazertinib. A substudy will enroll participants from Arms A and B who experience specific new-onset or persistent DAEIs (Grade \>=2) during treatment with intravenous (IV) amivantamab and lazertinib. This substudy aims to assess the reactive use of dermatologic treatment strategies in these participants.
Eligibility
Inclusion Criteria:
* Have histologically or cytologically confirmed, locally advanced or metastatic non-small cell lung cancer (NSCLC); Is treatment naive and not amenable to curative therapy including surgical resection or (chemo) radiation. Adjuvant or neoadjuvant therapy for Stage I, Stage II or Stage IIIA disease is allowed if last dose administered more than 12 months prior to the development of locally advanced or metastatic disease
* Have a tumor that harbors an epidermal growth factor receptor (EGFR) Exon 19del or Exon 21 L858R substitution, as detected by an Food and Drug Administration (FDA)-approved or other validated test in a clinical laboratory improvement amendments (CLIA)-certified laboratory (sites in the United States) or an accredited local laboratory (sites outside of the United States) in accordance with site standard-of-care
* A participant with asymptomatic or previously treated and stable brain metastases may participate in this study. Participants with a history of symptomatic brain metastases must have had all lesions treated as clinically indicated (that is, no current indication for further definitive local therapy). Any definitive local therapy to brain metastases must have been completed at least 14 days prior to randomization, and the participant can be receiving no greater than 10 milligram (mg) prednisone or equivalent daily for the treatment of intracranial disease
* Can have prior or concurrent second malignancy (other than the disease under study) which natural history or treatment is unlikely to interfere with any study endpoints, safety, or the efficacy of the study treatment(s). For the amivantamab SC expansion cohorts: Due to the increased risk of skin cancer with ruxolitinib, participants with any prior or concurrent skin malignancies will be excluded
* Sub-study: Participants must have new-onset or persistent (defined as non-responsive to standard of care \[SoC\]) Grade \>=2 specific DAEIs of the scalp, face, or body, as defined by NCI-CTCAE Grading v5.0 for DAEIs (excluding paronychia)
Exclusion Criteria:
* History of uncontrolled illness, including but not limited to uncontrolled diabetes; ongoing or active infection (includes infection requiring treatment with antimicrobial therapy \[participants will be required to complete antibiotics 1 week prior to starting background anticancer treatment\] or diagnosed or suspected viral infection). For the amivantamab SC expansion cohorts, this includes active localized serious infections; active bleeding diathesis; impaired oxygenation requiring continuous oxygen supplementation; refractory nausea and vomiting, chronic gastrointestinal diseases, inability to swallow the formulated product, or previous significant bowel resection that would preclude adequate absorption of background anticancer treatment or doxycycline/minocycline; psychiatric illness, social situation, or any other circumstances that would limit compliance with study requirements; any ophthalmologic condition that is clinically unstable; pre-existing skin condition that would prevent adequate evaluations of dermatologic toxicity, as determined by the investigator
* Medical history of interstitial lung disease (ILD), including drug-induced ILD or radiation pneumonitis
* Known allergy, hypersensitivity, or intolerance to the excipients of amivantamab, lazertinib, or to tetracyclines, doxycycline, minocycline, timolol\*, ruxolitinib\*, zinc\*, corticosteroids\* or their excipients or to any component of the enhanced dermatologic management (\*for the amivantamab SC expansion cohorts)
* Participant has received any prior systemic treatment at any time for locally advanced stage III B/C or metastatic stage IV disease (adjuvant or neoadjuvant therapy for stage I, II or IIIA disease is allowed if last dose administered more than 12 months prior to the development of locally advanced or metastatic disease)
* Participant has an active or past medical history of leptomeningeal disease
* Sub-study: Participants who have received prior treatment for epidermal growth factor receptor (EGFR)-induced DAEIs with JAK inhibitors (for Cohort A) or calcineurin inhibitors (for Cohort B)
Primary outcome measure(s)
- Number of Participants With Grade Greater Than or Equal to (>=) 2 Dermatologic Adverse Events of Interest (DAEIs) Within 12 Weeks After Initiation of Anticancer Treatment — Up to 12 weeks after initiation of anticancer treatment
Number of participants with Grade \>= 2 DAEIs within 12 weeks after initiation of anticancer treatment based on National Cancer Institute Common Toxicity Criteria for Adverse Events (NCI-CTCAE) Version (v) 5.0 will be reported. DAEIs includes rash, dermatitis acneiform, pruritus, skin fissures, acne, folliculitis, erythema, eczema, rash maculo-papular, skin exfoliation, skin lesion, skin irritation, dermatitis, rash erythematous, rash macular, rash popular, rash pruritic, rash pustular, dermatitis contact, dermatitis exfoliative generalized, drug eruption, dyshidrotic eczema, eczema asteatotic and paronychia. As per NCI CTCAE v 5.0, severity scale ranges from Grade 1 (mild) to Grade 5 (death). Grade 1= mild, Grade 2= moderate, Grade 3= severe, Grade 4= life-threatening, and Grade 5= death related to adverse event.
Trial sites (93)
| Facility | City | Region | Status |
| Ironwood Cancer and Research Center |
Chandler |
Arizona |
|
| City of Hope |
Duarte |
California |
|
| Providence Fullerton |
Fullerton |
California |
|
| Los Angeles Cancer Network |
Glendale |
California |
|
| City of Hope Seacliff |
Huntington Beach |
California |
|
| City of Hope Orange County Lennar Foundation Cancer Center |
Irvine |
California |
|
| City of Hope Long Beach Elm |
Long Beach |
California |
|
| Cancer and Blood Specialty Clinic |
Los Alamitos |
California |
|
| Keck Hospital of USC |
Los Angeles |
California |
|
| USC Norris Oncology Hematology Newport Beach |
Newport Beach |
California |
|
| Kaiser Permanente Oakland Medical Center |
Oakland |
California |
|
| Kaiser Permanente Roseville Medical Center |
Roseville |
California |
|
| Kaiser Permanente San Francisco Medical Center |
San Francisco |
California |
|
| Kaiser Permanente Santa Clara Medical Center |
Santa Clara |
California |
|
| City of Hope South Pasadena |
South Pasadena |
California |
|
| Kaiser Permanente Northern California |
Vallejo |
California |
|
| Kaiser Permanente Walnut Creek Medical Center |
Walnut Creek |
California |
|
| University Cancer & Blood Center |
Athens |
Georgia |
|
| Hope and Healing Care |
Hinsdale |
Illinois |
|
| Oncology Hematology Associates |
Springfield |
Missouri |
|
| Renown Health Medical Oncology |
Reno |
Nevada |
|
| Hunterdon Hematology Oncology |
Flemington |
New Jersey |
|
| Clinical Research Alliance Inc |
Westbury |
New York |
|
| Regional Medical Oncology Center |
Wilson |
North Carolina |
|
| University Hospitals Cleveland Medical Center |
Cleveland |
Ohio |
|
| Virginia Cancer Specialists |
Fairfax |
Virginia |
|
| Valley Medical Center |
Renton |
Washington |
|
| Gundersen Health System |
West Salem |
Wisconsin |
|
| Hospital Italiano de Buenos Aires |
Buenos Aires |
Argentina |
|
| IADT Instituto Argentino de Diagnostico y Tratamiento |
CABA |
Argentina |
|
| Centro Medico Austral |
Capital Federal |
Argentina |
|
| Hospital Italiano de La Plata |
La Plata |
Argentina |
|
| Hospital Privado de la Comunidad |
Mar del Plata |
Argentina |
|
| CTO Centro De Tratamento Oncologico LTDA |
Belém |
Brazil |
|
| Santa Casa de Misericordia de Belo Horizonte |
Belo Horizonte |
Brazil |
|
| Liga Paranaense de Combate ao Cancer |
Curitiba |
Brazil |
|
| Fundacao Doutor Amaral Carvalho |
Jaú |
Brazil |
|
| Hospital Nossa Senhora da Conceicao S A |
Porto Alegre |
Brazil |
|
| Nucleo de Oncologia da Bahia Oncoclinicas |
Salvador |
Brazil |
|
| Hospital Ana Nery Santa Cruz do Sul |
Santa Cruz do Sul |
Brazil |
|
+ 53 more sites — see the full list on the official registry below.
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